Aim. The duration of systemic antibiotic therapy following first-stage surgery is contentious. Our Institution's philosophy is to perform an aggressive debridement, use high concentration targeted antibiotics through cement beads and systemic prophylactic antibiotics alone. In the presence of significant soft tissue infection or microbiological diagnostic uncertainty; systemic antibiotics may be prescribed for 5 days whilst awaiting tissue culture results. The aim of this study was to assess the success of our philosophy in the management of PJI of the hip using our two-stage protocol. Method. A retrospective review of our Institution's prospectively-collected database was performed to identify those patients who were planned to undergo a two-stage hip revision procedure for PJI. All patients had a confirmed diagnosis of PJI as per the major criteria of MSIS 2013, a minimum 5-years follow up and were assessed at the time of review using the MSIS working group outcome-reporting tool (2018). They were then grouped into “successful” or “unsuccessful” (suppressive antibiotics, further revision for infection, death within 1 year). Results. 299 intended two-stage hip revisions in 289 patients (6 repeat ipsilateral two-stage, 4 bilateral two-stage) met our inclusion criteria. 258 (86%) patients proceeded to 2. nd. stage surgery. Median follow up was 10.7 years. 91% success rate was observed for those patients who underwent reimplantation; dropping to 86% when including the patients who did not proceed to second stage surgery. The median duration of post-operative systemic antibiotics following first stage surgery was 5 days (IQR 5–9). No significant difference in outcome was observed in patients who received either; < / = 48 hours (86%; n=70) compared to > 48 hours antibiotics (86%; n=229; p=0.96) or </= 5 days of antibiotics (88%; n=202) compared to > 5 days antibiotics (82%; p=0.38). A significant majority had gram-positive (88%) infection with 30% being polymicrobial. Greater success rates were observed for gram-positive PJI (87%); than for gram-negative PJI (84%) and mixed Gram infection (72%; p=0.098). Conclusion. Aggressive surgical debridement with high concentration, targeted local antibiotic delivery at time of first stage hip surgery, without prolonged systemic antibiotics, provides a high rate of success, responsible antibiotic stewardship and reduced hospital costs

The duration of systemic antibiotics following first-stage surgery is contentious. Our Institution's philosophy is to perform an aggressive debridement, high concentration of targeted antibiotics through cement beads and systemic prophylactic antibiotics alone. In the presence of significant soft tissue infection or microbiological diagnostic uncertainty; systemic antibiotics may be prescribed for 5 days whilst awaiting tissue culture results. The aim of this study was to assess the success of our philosophy for two-stage hip revision. A retrospective review of our Institution's prospective database was performed to identify all intended two-stage hip revision procedures for PJI. All patients had a confirmed PJI as per MSIS 2013 criteria, minimum 5-years follow up and outcomes according to the MSIS working group outcome-reporting tool; then grouped into “successful” or “unsuccessful” (suppressive antibiotics, further revision for infection, death within 1 year). 383 intended two-stage hip revisions were identified; of which 299 met our inclusion criteria, in 289 patients (6 repeat ipsilateral two-stage, 4 bilateral two-stage). Median follow up was 10.7 years (IQR 6.3 – 15.0). 258 (86%) patients proceeded to 2. nd. stage surgery. 91% success rate was observed for those patients who underwent reimplantation, although dropping to 86% when including the patients who did not proceed to second stage. The median duration of post-operative systemic antibiotics was 5 days (IQR 5–9). No significant difference was observed in patients who received either; < / = 48 hours (86%; n=70) compared to > 48 hours antibiotics (86%; n=229; p=0.96) or </= 5 days of antibiotics (88%; n=202) compared to > 5 days antibiotics (82%; p=0.38). A significant majority had gram-positive (88%) infection with 30% being polymicrobial. Greater success rates were observed with two-stage exchange or gram-positive PJI (86%); than for gram-negative PJI (81%) and polymicrobial infection (74%) (p=0.36). Fungal PJI was observed to have a significantly reduced rate of success (n=3; 33%; p=0.03). Aggressive surgical debridement with high concentration, targeted local antibiotic delivery at time of first stage to manage PJI of the hip provides a high rate of success, responsible antibiotic stewardship and reduced hospital costs

Purpose. To analyze the effectiveness of a vancomycin impregnated calcium sulfate cement bead insertion after debridement (of) an acute-immediate stage infected hip arthroplasty. Materials and Methods. Between 2002 and 2008, 13 patients with documented acute-immediate stage infection of hip arthroplasty were reviewed and followed for at least two years postoperatively(average 4.3 years). The preoperative and postoperative clinical and radiologic findings and blood laboratory work were checked. All cases were performed through retention of the implant and massive debridement and saline irrigation. After that a vancomycin impregnated calcium sulfate cement beads was inserted. Results. After the first operation, the average interval for second operation was 27.7 days (17–37). At the second operation, the erythrocyte sediment rate and C-reactive protein were 150.97 mm/hr (34.6 ∼339.7 mm/hr) and 76.4 mg/L (41∼132 mg/L) respectively. Infectious organism were cultured and isolated. There were 5 cases of Methicillin resistant staphylococcus aureus (MRSA). In addition, results of an antibiotics sensitivity test were 8 cases of Vancomycin, and 5 cases of 3rd generation Cephalosporin. Radiologic results showed 10 cases with stable fixation on last follow-up (femoral stem) and 1 case of hip joint space narrowing, acetabular erosion. Conclusion. Vancomycin impregnated, calcium sulfate, cement bead insertion for an acute immediate infection of hip arthroplasty proved to be a useful method

Summary Statement. Conventional culture techniques have poor sensitivity for detecting bacteria growing in biofilms, which can result in under-diagnosis of infections. Sonication of biofilm colonised orthopaedic biomaterials can render bacteria in biofilm more culturable, thereby improving diagnosis of orthopaedic implant infections. Introduction. Prosthetic joint infection (PJI) is a potentially devastating complication in arthroplasty. Biofilm formation is central to PJI offering protection to the contained bacteria against host defence system and antimicrobials. Orthopaedic biomaterials generally have a proclivity to biofilm colonisation. Conventional culture technique has a low sensitivity for detecting bacteria in biofilm. Sonication can disrupt bacteria biofilms aggregations and dislodge them from colonised surfaces, rendering them culturable and consequently improve the diagnosis of otherwise culture-negative PJI. We investigated the effect of ultrasonication on biofilms adherent to poylmethylmethacrylate PMMA cement. Method. Identical PMMA cement beads were aseptically prepared using 7mm bead templates. Each sample comprised of two beads and with multiple replicates made for each sample. Two proficient biofilm forming strains of Staphylococcus epidermidis (5179-R1 and 1457) were used for the experiments. Each set of cement sample was immersed in Brain Heart Infusion broth inoculated with a pre-culture of the chosen bacteria strains (final concentration approximately 4 × 10. 6. CFU/ml). All samples were then incubated for 24 hours at 37°C to allow for biofilm growth and colonisation of the cement surfaces, as well as for biofilm maturity. After incubation, each sample was washed twice with sterile phosphate buffer saline (PBS) to remove non-adherent and loosely adherent bacteria. The cement beads were transferred to a fresh sterile bottle at each stage of the experiment, while ensuring the maintenance of asepsis. After the final wash, 10ml of sterile PBS was added to the cement beads and each sample was sonicated for varying periods: 0min, 5min, 10min, 20min and 40min. Sonicate fluid were collected after each period of sonication, with which culture plates were inoculated for the purpose of viable bacteria counting. Results. The optimum sonication period was between 5min and10 min. The mean pre-sonication CFU/ml were 4.7 × 10. 5. and 8.3 × 10. 5. for bacteria strains 5179-R1 and 1457 respectively, while the mean CFU/ml after 10min of sonication were 1.4 × 10. 7. and 0.74 × 10. 7. for bacteria strains the respective bacteria strains. Discussion / Conclusion. Our study showed a significant increase (almost 100 fold) in bacteria culture yield following sonication. We were also able to demonstrate that the optimum duration for sonication (using comparable sonicators) was approximately 10min. Sonication was able to completely remove adherent bacteria from the surfaces of our cement samples allowing them to be cultured. Our result suggests that sonication of bone cement can be instrumental in improving the diagnosis of biofilm associated PJI

Aims. High-energy injuries can result in multiple complications, the most prevalent being infection. Vancomycin powder has been used with increasing frequency in orthopaedic trauma given its success in reducing infection following spine surgery. Additionally, large, traumatic injuries require wound coverage and management by dressings such as negative pressure wound therapy (NPWT). NPWT has been shown to decrease the ability of antibiotic cement beads to reduce infection, but its effect on antibiotic powder is not known. The goal of this study was to determine if NPWT reduces the efficacy of topically applied antibiotic powder. Methods. Complex musculoskeletal wounds were created in goats and inoculated with a strain of Staphylococcus aureus modified to emit light. Six hours after contaminating the wounds, imaging, irrigation, and debridement and treatment application were performed. Animals received either vancomycin powder with a wound pouch dressing or vancomycin powder with NPWT. Results. There were no differences in eradication of bacteria when vancomycin powder was used in combination with NPWT (4.5% of baseline) compared to vancomycin powder with a wound pouch dressing (1.7% of baseline) (p = 0.986), even though approximately 50% of the vancomycin was recovered in the NPWT exudate canister. Conclusion. The antimicrobial efficacy of the vancomycin powder was not diminished by the application of NPWT. These topical and locally applied therapies are potentially effective tools that can provide quick, simple treatments to prevent infection while providing coverage. By reducing the occurrence of infection, the recovery is shortened, leading to an overall improvement in quality of life. Cite this article: Bone Joint Res 2021;10(2):149–155

Aim. To evaluate the ability of different combinations of antibiotic loaded cement to inhibit bacteria growth and biofilm formation. Method. Cement beads were aseptically prepared using Palacos R (plain 40g PMMA cement) or Palacos R+G (40g PMMA cement containing industrially added 0.5g of gentamicin), with or without supplementary antibiotics as follows: Palacos R; Palacos R+G; Palacos R plus 1g / 2g daptomycin; Palacos R+G plus 1g / 2g of daptomycin; Palacos R plus 1g / 2g vancomcyin; and Palacos R+G plus 1g / 2g vancomycin. After production, each antibiotic loaded acrylic cement (ALAC) combination was allocated into two groups (group 1 and 2). The group 2 cement beads were initially eluted in broth at 37. o. C for 72hours then transferred to fresh broth containing a known concentration of bacteria. The group 1 samples were not eluted but directly immerse in culture broth containing bacteria. All samples were thereafter incubated at 37. o. C for 24 hours. After incubation, group 1 samples were visually assessed for bacterial growth, while for the group 2 samples, biofilm formation were quantified using ultrasonication and viable bacteria counting technique. Three proficient biofilm forming Staphylococcus epidermidis bacterial strains (1457, 1585-RA and 5179-R1) were used for all experiments and the bacteria counts were expressed as colony forming units / ml (CFU/ml). Results. In the group 1 samples, all the ALAC combinations were able to inhibit growth of all the three biofilm bacteria strains assessed except the gentamicin only samples in which biofilm growth were observed within 24hours. Meanwhile, in group 2, bacterial growth and biofilm formation by all three bacterial strains were observed on all the ALAC combinations, with the least biofilm formation being on the Palacos R+G plus 2g daptomycin combinations (mean CFU/ml: 1.04E +06) and the greatest on the gentamicin only cement (mean CFU/ml: 2.3E +07). Conclusions. Our study demonstrates that the highest antimicrobial activity of ALAC is seen in the first 24 hours. However, after 72 hours of antibiotic release, fresh bacterial exposure in fresh broth resulted in varying degrees of biofilm colonisation of all ALAC surfaces. Nonetheless, the overall biofilm formation was least on the gentamicin / daptomycin combinations and the results were statistically significant when compared to plain cement (p < 0.05, two tail t-test)

Introduction. Periprosthetic joint infection (PJI) remains the main cause of failure in primary and revision total knee arthroplasties (TKAs). Local delivery of antibiotics, mainly antibiotic-loaded bone cement (ALBC), is commonly employed to prevent PJI. Over the past decade, tantalum and porous titanium have been successfully utilized as metaphyseal fixation devices to address bone loss and improve biologic fixation during revision TKA. However, no study has examined the antimicrobial properties compared to bone cement. The purpose of this study was to compare the ability of tantalum, 3D porous titanium, antibiotic-loaded bone cement (ALBC) and smooth titanium alloy (STA) to inhibit Staphylococci bacterial agents in an in vitro medium environment, based on the evaluation of the zone of inhibition (ZOI) and the antibacterial activity duration. Our study hypothesis was that we will found no significant difference between groups to inhibit Methicillin-Sensitive or Methicillin-Resistant Staphylococcus aureus (MSSA/MRSA) agents. Methods. Thirty beads made of 3 different materials (tantalum/ 3D porous titanium/ STA) were bathed during 1hour inside of a solution made of 1g vancomycin with 20-mL of sterile water for injection (bath concentration: 50 mg/mL). Ten 1cm. 3. cylinders were also created mixing standard surgical cement with 1g of Vancomycin in standardized sterile molds (ALBC beads). Finally, thirty beads made of tantalum/ 3D porous titanium/ STA were bathed in phosphate buffered saline solution to act as a control group. Cylinders were then placed on agar plates inoculated with MSSA and MRSA. Inhibition zone diameters were measured each day and cylinders were transferred onto a new inoculated plate. Inhibition zones were measured with a manual Vernier caliper and with automated software. The mean inhibition zones between groups were compared using the Wilcoxon Test. Results. The inter-class coefficient correlation values indicated an optimal intra-observer and inter-observer reproducibility for ZOI measurement (ICC 0.96 and ICC 0.98). For MSSA and MRSA, no inhibitory effect was found in the control group and antibiotic-loaded STA beads exhibited a short inhibitory effect until day 2. For MSSA, both tantalum and 3D porous titanium beads exhibited larger inhibition zones than cement beads (all p<0.01) each day until day 7 for tantalum and until day 3 for 3D porous titanium. After 6 days, ALBC presented larger inhibition zone than the 3D porous titanium, but no difference was found with tantalum. For MRSA, both tantalum and 3D porous titanium beads had significantly larger inhibition zones than ALBC each day until day 6 for tantalum (all p<0.01) and until day 3 for 3D porous titanium (all p<0.04). ALBC presented larger inhibition zone than tantalum and 3D porous titanium from day 7 to 9 (all p<0.04). Conclusion. Our results demonstrate that porous metal implants can deliver local antibiotics over slightly varying time frames based on our in vitro analysis. Antibiotic-impregnated tantalum and 3D porous titanium constructs exhibited superior antimicrobial properties when compared to STA. Future goals include impregnating porous metals with antibiotics for intraoperative use during revision TKA. For figures, tables, or references, please contact authors directly

Introduction. Vancomycin is commonly added to acrylic bone cement during revision arthroplasty surgery. Proprietary cement preparations containing vancomycin are available but significantly more expensive. We investigated whether the antibiotic elution and mechanical strength of ‘home-made’ vancomycin containing bone cement was comparable to commercial vancomycin-impregnated cement. Methods. A total of 18 cement discs of constant size, containing either proprietary CopalG+V. ®. ; or ‘home-made’ CopalR+G. ®. with vancomycin added by hand, were made. Each disc contained the same antibiotic quantities (0.5g gentamycin, 2g vancomycin) and was immersed in ammonium acetate buffer in a sealed container. Fluid from each container was sampled at eight time points over a two week period. The concentration of gentamicin and vancomycin in the fluid was analysed using high performance liquid chromatography mass spectrometry. The impact strength of each PMMA cement preparation was measured using a Charpy-type impact tester. Results. Highest peak antibiotic concentrations were observed from the ‘home-made’ vancomycin containing cement, added as in the operating theatre. Overall antibiotic elution was, five-fold (vancomycin) and two-fold (gentamicin), greater from the ‘home-made’ mix compared to commercially mixed cement. However the ‘home-made’ cements showed greater variation in elution kinetics compared to the commercial mix. Use of a vacuum during mixing had no significant effect on antibiotic elution in any of the samples. Impact strength testing showed no significant differences between the groups. Discussion. Our findings suggest the addition of 2g vancomycin powder to gentamicin-impregnated bone cement in theatre, significantly increases elution of both antibiotics, with no significant loss of strength, compared to commercially prepared cement. Conclusion. We have found no significant advantages of expensive off-the-shelf vancomycin-impregnated bone cement and recommend the addition of vancomycin powder by hand when making cement beads and spacers

Introduction:. The developing world often lacks the resources to effectively treat the most serious injuries, potentially resulting in severe complications of orthopaedic trauma, including osteomyelitis following open fractures or surgical fracture treatment. Antibiotic cement beads are now a widely accepted method of delivering antibiotics locally to the infected area following trauma. This study is based in Cambodia, a low income country struggling to recover from a recent genocide. Aims:. This project studied the effectiveness of locally made antibiotic beads, analysing their effectiveness after being gas sterilised, packaged and kept in storage. Methods:. Different antibiotic beads were manufactured locally using Simplex cement and tested against MRSA bacteria grown from a case of osteomyelitis. Each antibiotic was tested before and after a process of gas sterilisation as well as later being tested after storage in packaging up to 42 days. Results:. The gentamicin, vancomycin, amikacin and ceftriaxone beads all inhibited growth of the MRSA on the TSB and agar plates, both before and after gas sterilisation. All four antibiotics continued to show similar zones of inhibition after 42 days of storage, with slight fluctuations from week to week. Conclusion:. The four antibiotic beads manufactured using limited resources and in the austere environment were all effective in inhibiting bacterial growth. The growth of MRSA was inhibited by the antibiotic beads. Gas sterilisation or storage at room temperature for up to 42 days did not adversely deteriorate the efficacy of the beads. The results show significant promise to produce beads with locally obtainable ingredients in an austere environment and improve cost effectiveness by storing them in a sterilised condition

Prosthetic joint infection(PJI) still remains a concern in orthopaedic practice. Antibiotic-loaded acrylic-cement(ALAC) is a proven means of lowering the incidence of PJI. However, increasing antimicrobial resistance has complicated both prophylaxis and treatment, prompting the use of combination antimicrobial therapy, with the addition of vancomycin to gentamicin-containing ALAC commonly used. The new antimicrobial, daptomycin, has better activity than vancomycin and we studied its elution from ALAC in comparison with vancomycin, along with its impact on the co-elution of gentamicin. Cement beads were prepared from PalacosRG containing, 1g/2g daptomycin, 1g/2g vancomycin and without additional antibiotics. Six replicates of each combination were eluted in PBS at 37oC, at timed intervals, for up to 90days, the antibiotic loss was assessed using validated assays. The mean recovery of gentamicin after 90days was 1.1mg with half eluted within the first 6 hours. Recovery was significantly increased by 60% and 40% with addition of 1g&2g of daptomycin(two-tail t-test: p=0.004 and p=0.02), respectively. Although there was a slight increase in gentamicin recovery in vancomycin loaded samples, this was not statistically significant(p>0.05). The significant increases in gentamicin elution from Palacos RG when supplemented with daptomycin, along with a superior activity, may provide a better synergistic effect than PalacosRG supplemented with vancomycin in the management of PJI

Introduction. Antibiotic-loaded acrylic cement (ALAC) is employed in the treatment or prevention of infected total hip arthroplasty (THA). We have administered vancomycin (VCM) as the ALAC for the treatment of THAs with methicillin-resistant Staphylococcus aureus, or for the prevention of THAs with high risks. This study aimed to evaluate the serum concentration of VCM from ALAC in THA or cement beads. Methods. Between December 2013 and February 2014, 16 hips (16 patients) underwent application of the ALAC including VCM at our institution. Two hips were used for the treatment of infection, in the first stage of two-staged revision THAs (i.e., cement beads). Two hips were used for the both treatment and prevention of infection, in one-staged revision THAs. Twelve hips were used for the prevention of infection, in aseptic revision THAs or primary THAs with high risks. Patients were classified into two groups depending on the VCM concentration of ALAC, as follows: high-dose group (2 hips), average 4.4% (3.8–5.0%); low-dose group (14 hips), average 1.6% (1.3–2.5%). The amount of VCM placed as ALAC into the hip was calculated by using the remaining ALAC. The serum concentration of VCM was evaluated at 1 day, 4 days, 7 days, and 28 days after surgery. Statistical analysis was performed by using the t-test, and the differences were considered significant when the p value was <0.05. Results. Average amount of VCM placed as ALAC was 3.5 g (3.1–4.0 g) and 0.9 g (0.3–2.0 g) in the high- and low-dose groups, respectively. The average serum concentration of VCM (μg/mL) was 2.5 and 1.1 on day 1, 2.8 and 1.2 on day 4, 2.3 and 1.1 on day 7, and 1.9 and 1.0 on day 28, in the high- and low-dose groups, respectively. There were significant differences in the high- and low-dose groups on all days. Conclusions. Although the serum concentration of VCM in the high-dose group is significantly increased compared to that in the low-dose group, it is always under the effective blood concentration (5–10 μg/mL) and seem to be clinically safe. Further, we confirmed the continuous effect of ALAC, including VCM, because they were detected at 28 days. However, careful continued follow-up and further evaluation will be required

Introduction. We report our mid-term results and risk factors of a two-stage revision using impaction bone grafting for an infected hip replacement. Methods. A two-stage revision using impacted cancellous allografs and cement was performed in 13 patients (7 total hip replacements, 6 femoral head replacements) with confirmed infection. The mean age of the patients at first stage operation was 63 years (range, 45–84 years). In the first stage, local antibiotics were added to customized cement beads and/or a cement spacer after removal of all components and radical debridement. In the second stage, impaction grafting was done using the X-change system (Exeter). Results. Of the patients, 8 underwent multiple operations to obtain evidence that infection had been overcome in the first stage, and of them, 6 had infection due to methicillin-resistant Staphylococcus aureus (MRSA). The mean duration from first stage operation to second stage revision was 8 months (range, 3–17 months). Only one patient suffered re-infection due to MRSA after second stage revision, which was not the original infecting agent, and the other 12 patients had satisfactory radiological outcomes. The success rate was 92% at the mean follow-up of 4 years (range, 1–10 years) after revision. Conclusion. Allograft bone was shown to be useful for infected hip replacement with a considerable loss of bone stock. We considered that control of MRSA infection is a key factor for successful outcome

Introduction. Infection following traumatic injury of the tibia is challenging, with surgical debridement and prolonged systemic antibiotic therapy well established. Local delivery via cement beads has shown improved outcome, but these often require further surgery to remove. Osteoset-T is a bone-graft substitute composed of calcium sulphate and 4%-Tobramycin, available in pellets that are packed easily into bone defects. Concerns remain regarding the sterile effluent produced as it resorbs, along with the risk of acute kidney injury following systemic absorption. Purpose. We present outcomes of 22 patients treated with Osteoset-T. Methods. Medical notes were reviewed of every case of osteomyelitis of the tibia over a 30-month period, in which Osteoset-T had been used. Excision of infected soft tissue and tibial debridement was performed. Metalwork whenever present removed, before Osteoset-T pellets were packed into any cortical defects or the intra-medullary canal. Further stabilisation (n=9) and soft tissue reconstruction (n=7) was undertaken as required. Intravenous vancomycin and meropenem was administered after sampling. Meropenem discontinued after 3 days if no gram negatives cultured, and vancomycin continued for 1 week. Thereafter targeted antibiotic therapy given for 6 weeks, or ciprofloxacin and rifampicin orally if no growth. Results. Average follow-up was 16 months, with wound complications encountered in 50%. A wound discharge in the early post-operative period was noted in 8 patients (36%) independent of site of Osteoset-T placement, with 6 demonstrating wound healing complications. Whereas only 5 of 14 patients without wound leak developed wound complications, but the difference did not reach significance (p=0.18, Fisher exact test). Union rate and infection eradication was 100%, with only one patient developing a transient acute kidney injury. Conclusion. Despite a high incidence of wound discharge that may promote healing complications, Osteoset-T is an effective adjunct in treatment of chronic tibial osteomyelitis following trauma, with nephrotoxicity concerns not warranted

Aims

The burden of revision total hip arthroplasty (rTHA) continues to grow. The surgery is complex and associated with significant costs. Regional rTHA networks have been proposed to improve outcomes and to reduce re-revisions, and therefore costs. The aim of this study was to accurately quantify the cost and reimbursement for a rTHA service, and to assess the financial impact of case complexity at a tertiary referral centre within the NHS.

Background and purpose: Commercial gentamicin-loaded bone cement beads (Septopal. ®. ) constitute an effective delivery system for local antibiotic therapy. However, these beads are not commercially available in all parts of the world, and are too expensive for common use in others. Therefore, orthopedic surgeons worldwide make antibiotic-loaded beads themselves. However, these beads are usually not as effective as the commercial beads because of inadequate release kinetics. The aim of this study was to develop a simple, cheap and effective formulation to prepare gentamicin-loaded beads with release properties and antibacterial efficacy similar to the ones of commercially available beads. Methods: Acrylic beads were first prepared with variable monomer contents: 500 μl/g polymer (100%), 375 μl/g polymer (75%), and 250 μl/g polymer (50%) to increase gentamicin release through the creation of a less dense polymer matrix. After optimal monomer content was defined, different gel-forming polymeric fillers were added to enhance the permeation of fluids into the beads. Polyvinylpyrrolidone (PVP) 17 was selected as a suitable filler, its concentration was varied and the antibiotic release and antibacterial efficacy of the final beads were compared with the ones of Septopal. ®. beads. Results: Gentamicin release rate and extend of release from beads prepared with 50% monomer increased upon increasing the PVP 17 content in the beads. Beads with 15 w/w% PVP 17 released 87% of their antibiotic content within 336 h. Importantly, this is significantly more than the gentamicin-release from Septopal. ®. beads, that appeared confined to only 59% within 336 h. In addition, acrylic beads with 15 w/w% PVP 17 reduced bacterial growth up to 93%, which is a similar reduction as achieved with Septopal. ®. . Interpretation: A simple, cheap and effective formulation and preparation process has been described for hand-made gentamicin-releasing acrylic beads, with release kinetics and antibacterial efficacy similar to the ones of commercially available Septopal. ®. beads

Aim: Prosthetic loosening has emerged as a most serious long-term complication after Joint Arthroplasty and the most common cause for revision. Arthroplasty is performed either under a general anaesthesia or a spinal/ epidural or a combination of the two. During general anaesthesia Sevoßurane is used for induction and maintenance. We investigated the effect of Sevoßurane on bone cement in an in vitro setting. Materials & Methods:. 40 beads of roughly the same size were prepared from 2 mixes in a sterile condition in vacuum. 20 of these beads were scanned initially under an electron microscope at 2 levels of magniþcation. The surface images of all the cement beads were analysed. Equal numbers of scanned and unscanned beads were separated into 2 groups of 20 each. They were immersed into 2 jars of normal saline. One was connected to the anaesthetic apparatus and exposed to Sevoßurane at a concentration of 2.5%. The other group (control) was exposed to oxygen. This was performed for 2 hours in an orthopaedic theatre. All the beads were then scanned. Results & Conclusions: The post Sevoßurane exposure images revealed a large number of pits of irregular dimensions on the surface. There were no changes on the surface of control beads. This suggests that in clinical concentrations Sevoßurane can affect the surface of bone cement and its mechanical properties. This can in turn affect the bone cement interface and be a potential cause of prosthetic loosening

Deep periprostheses infection is a devastating complication that occurred in 8 to 20% of patients treated by en bloc resection and prosthetic reconstruction for bone sarcomas. The systemic safety of high dose vancomycin loaded spacer has been investigated but rarely the elution of vancomycin in vivo. The aim of the study is to evaluate the elution of vancomycin into the site of the excision arthroplasty to see if effective bactericidal activity can be obtained. Patients and Methods: From 2006 to 2008, 16 consecutive patients were managed by prosthetic exchange procedure using high dose vancomycin loaded cement. Patients were males :7, females :9. Average of age at the time of surgery was 22 years. Antibiotic-loaded methylmethacrylate cement beads were prepared by adding 4 g of vancomycin powder to a 40 g pack of Palacos R cement in the operative place immediately before the operation. We used 4 G vancomycin per batch of 40 G cement and generally used 2 to 4 batches of cement in one spacer depending of the size and length of resection. The average dose of vancomycin was 7.5 G (4–14.5). The wounds were closed with absorbable mono-filaments sutures over one suction drain. Intravenous antibiotics excluding vancomycin were given for 6 to 24 weeks. Patients biological values and the concentrations of vancomycin in the blood and in the aliquots of suction drainage were checked daily until removal of drain. Vancomycin was measured by fluorescent polarization immunoassay on the AxSYM analyzer (Abbott). Results: the serum concentration of vancomycin remained in all patients under 2 μg/ml confirming the systemic safety of the method. Local concentration of vancomycin depended of the dose of vancomycin used and decreased quickly during the first week: half life :2.25 days. For a dose of 10 G vancomycin, the average concentration in the liquid from the drain was :. d1 :725μg/ml. d2 :510 μg/ml. d3 :346 μg/ml. on day 10, its remained over 35μg/ml vancomycin in the aliquot of the drain. These results should be compared to the bactericidal concentration of vancomycin for staphylococcus aureus:10 to 20 μg/ml for usual organisms, 20 to 40 for resistant organisms. We had no reported cases of allergy, toxicity or intolerance. Conclusion : high dose vancomycin spacers result in very low serum concentration without risk of systemic toxicity. In the operative wound, very high concentration are obtained, 10 to 20 fold bactericidal concentration for staphylococcus aureus. Additional studies are needed, with longer follow-up to evaluate the clinical efficacy of this method

Aims

Periprosthetic joint infection (PJI) occurs in approximately 1% to 2% of total knee arthroplasties (TKA) presenting multiple challenges, such as difficulty in diagnosis, technical complexity, and financial costs. Two-stage exchange is the gold standard for treating PJI but emerging evidence suggests 'two-in-one' single-stage revision as an alternative, delivering comparable outcomes, reduced morbidity, and cost-effectiveness. This study investigates five-year results of modified single-stage revision for treatment of PJI following TKA with bone loss.

Aim. Bacterial biofilms play a key role in prosthetic infection (PI) pathogenesis. Establishment of the biofilm phenotype confers the bacteria with significant tolerance to systemic antibiotics and the host immune system meaning thorough debridement and prosthesis removal often remain the only possible course of treatment. Protection of the prosthesis and dead-space management may be achieved through the use of antibiotic loaded cements and beads to release high concentrations of antibiotics at the surgical site. The antibacterial and antibiofilm efficacy of these materials is poorly understood in the context of mixed species models, such as are often encountered clinically. Methods. A P. aeruginosa and S. aureus in vitro co-culture biofilm model was grown using 1/5th BHI supplemented with 20 µM hemin. The ability of beads made from a synthetic calcium sulfate (CaSO4) loaded with vancomycin, tobramycin and vancomycin & tobramycin in combination to prevent biofilm formation and kill established co-culture biofilms were assessed using viable cell counts and confocal scanning laser microscopy (CSLM) over a 7 day time course. To assay for genetic changes to the individual species as a result of their presence together within a biofilm, mutation rates were measured using fluctuation analysis following growth as planktonic and biofilm cultures, alone or in co-culture. Mutants were determined based on their ability to grow on agar plates containing an inhibitory concentration of rifampicin. Mutation rates were calculated using the Ma-Sandri-Sarkar Maximum Likelihood Estimator and 94% confidence intervals compared for significance. Results. Mixed species biofilms displayed differential sensitivity to vancomycin alone and tobramycin alone CaSO4-loaded beads relative to single species biofilms. Preliminary data suggests 10- and 100-fold increase in mutation rates of P. aeruginosa and S. aureus, respectively, when in a co-culture relative to monospecies biofilm which, while further work is needed, may directly or indirectly contribute to the differing antibiotic sensitivities observed. A broad-spectrum intervention of CaSO4-loaded vancomycin & tobramycin beads was able to prevent bacterial colonisation and attenuate P. aeruginosa and S. aureus mixed species biofilm formation for multiple days. Conclusions. Synthetic antibiotic-loaded CS beads, with a broad-spectrum antibiotic combination, have potential to reduce or eliminate mixed species biofilm formation on implant material by providing locally high concentrations over sufficient time periods to aid in the management of PIs. * Stimulan, Biocomposites Ltd

Introduction and Aims: Endoprosthetic replacement (EPR) following Bone Tumor excision is common. A major complication is infection with serious consequences. The aim is to investigate the cause of infection, management and sequalae. Method: Over 11, 000 patients have been treated in our unit over 35 years. Information collected prospectively on a database, includes demographic data, diagnosis, treatment (including adjuvant), complications, and outcomes. Data was analysed to identify any infection in EPRs, its management and outcome. Factors such as operating time, blood loss, adjuvant therapy, type of prosthesis were investigated. Outcomes of treatment options were evaluated. Results: Data was analysed on 1265 patients undergoing EPR over 34 years. Giving a total follow-up time of over 6500 patient years. One hundred and thirty-seven (10.8%) patients had deep infection (defined by a positive culture [n=128] or a clinically infected prosthesis with pus in the EPR cavity [n=9]). Forty-nine (34%) required amputations for uncontrollable infection. The commonest organisms were Coagulase Negative Staphylococcus, Staphylococcus aureus and Group D Streptococci. The only satisfactory limb salvaging operation was two-stage revision, with a 71% success in curing infection. Systemic antibiotics, antibiotic cement or beads and surgical debridement had little chance of curing infection. Infection rates were highest in tibial (23.1%) and pelvic (22.9%) EPRs (p< 0.0001). Patients who had pre- or post-operative radiotherapy had significantly higher rates of infection (p< 0.0001), as did patients with extendable EPRs (p=0.007). Patients who had subsequently undergone patella resurfacing and rebushing also had a higher rate of infection (p= 0.019 & p=0.052). Conclusion: Infection is a serious complication of EPRs. Treatment is difficult and prolonged. Two-stage revision is the only reliable method for limb salvage following deep infection. Prevention must be the key to reducing the incidence of this serious complication